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R H Dowling

Publications and source records attributed to R H Dowling.

At least 19 recordsLinked to original sources
PubMed1997

Cholylglycine hydrolase and 7alpha-dehydroxylase optimum assay conditions in vitro and caecal enzyme activities ex vivo.

Increasing evidence implicates deoxycholic acid (DCA) in the pathogenesis of cholesterol-rich gallbladder stones. However, relatively little is known about the activities of the two intestinal bacterial enzymes (cholylglycine hydrolase and cholic acid 7alpha-dehydroxylase) responsible for the deconjugation and subsequent dehydroxylation of conjugated cholic acid (CA), to form DCA. We, therefore, established optimal reaction conditions for measuring the activities of these two enzymes in vitro, and applied these conditions to the determination of the enzymes in caecal aspirates from six subjects undergoing clinically-indicated colonoscopy. With respect to cholylglycine hydrolase activity: zero order kinetics were found over 20 min at 37 degrees C (pH optimum 4.0), with Km and Vmax values of 1.66 mmol/l and 0.90 mmol CA min(-1) mg prot(-1), respectively. For cholic acid 7alpha-dehydroxylation: zero order kinetics were found over 7.5 min at 37 degrees C, under anaerobic conditions (pH optimum 8.0), with Km and Vmax values of 5.23 x 10(-8) mol/l and 1.88 x 10(-7) mol DCA min(-1) mg prot(-1), respectively. Applying these reaction conditions to the caecal aspirates, endogenous cholylglycine hydrolase activities ranged from 0.49 to 2.43 units (mg protein[-1] min[-1]) and CA 7alpha-dehydroxylase activities from 1.75 to 5.82 x 10(-7) units (mg protein[-1] min[-1]). This study is unique in assaying quantitatively both the deconjugation and dehydroxylation enzyme activities in human caecal samples--an essential first step to further studies of intestinal bacterial enzymes in the pathogenesis of cholesterol gallstone disease.

Amidohydrolases↗
PubMed1997

Gallstone dissolution with oral bile acid therapy. Importance of pretreatment CT scanning and reasons for nonresponse.

In patients with cholesterol-rich gallbladder stones and a patent cystic duct, complete stone clearance rates of 65-90% have been reported with oral bile acids (OBAs) alone or with adjuvant lithotripsy (extracorporeal shock-wave lithotripsy; ESWL). The aims of the present study were to analyze pretreatment gallstone characteristics that predict the speed and completeness of dissolution with OBAs +/- ESWL, and to assess, in patients with incomplete dissolution, the reasons for the poor response. We compared pretreatment gallstone characteristics in 43 patients who became stone-free after a median of 9 months OBAs +/- ESWL with those in 43 age- and sex-matched patients whose stones failed to dissolve after two years of treatment. In those with incomplete gallstone dissolution, we repeated the oral cholecystogram and computed tomogram (CT) and, in selected patients, obtained gallbladder bile by percutaneous fine-needle puncture. In patients who became stone-free, those with stones that were isodense with bile and/or had CT scores of < 75 Hounsfield units had the fastest dissolution rates. In the 43 nonresponders, the main causes for treatment failure were impaired gallbladder contractility and acquired stone calcification. CT-lucent, noncholesterol stones, or failure of desaturation of bile with the prescribed bile acids, occurred in a minority. We conclude that the pretreatment CT attenuation score predicts both the speed and completeness of gallstone dissolution. In patients with incomplete stone dissolution, the combination of oral cholecystography, CT, and analysis of gallbladder bile will determine the underlying reasons for treatment failure in most, but not all, cases.

Administration, Oral↗
PubMed1996

Plasma arachidonic acid-rich phospholipids in Crohn's disease: response to treatment.

1. Increased concentrations of plasma polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease. However, it is not known whether there are corresponding changes in circulating phospholipids--the major source of fatty acids in the plasma. 2. Fasting plasma samples were obtained from 17 control subjects and 13 patients with active Crohn's disease [Simple Index of Crohn's Disease Activity (SICDA) > 6] before, and 2 and 8 weeks after, treatment with either a peptide diet or oral prednisolone. 3. Before treatment, the Crohn's disease patients had mildly active disease (SICDA 9.9 +/- 0.8, erythrocyte sedimentation rate 26.4 +/- 6.5 mm/h, serum C-reactive protein 2.8 +/- 0.4 mg/l). The proportions of the polyunsaturated phosphatidylcholine species, 16:0-20:4 (10.0 +/- 0.7%) and 16:0-22:6 (7.1 +/- 0.8%), were both significantly higher than those in healthy controls (7.6 +/- 0.5%, P < 0.01 and 5.3 +/- 0.5%, P < 0.05 respectively). 4. After 2 weeks treatment, the SICDA in the Crohn's disease patients decreased to 3.2 +/- 0.6 (P < 0.0001 compared with the pretreatment value), and there were corresponding falls in the erythrocyte sedimentation rate (to 12.6 +/- 2.7 mm/h, P < 0.05) and C-reactive protein concentration (to 1.7 +/- 0.3 mg/l, P < 0.05)--these improvements being maintained at 8 weeks. There was also a fall to normal values in 16:0-20:4 (to 7.7 +/- 0.6%, P < 0.01 compared with the pretreatment value) and in 16:0-22:6 (to 5.7 +/- 0.5%, P not significant), by week 8. 5. The proportions of polyunsaturated phosphatidylcholine molecular species were increased in the plasma of patients with active Crohn's disease, but fell to normal levels during disease remission. These observations are consistent with the theory that, in active Crohn's disease, the mucosal phospholipids containing polyunsaturated fatty acids are increased, contribute to eicosanoid synthesis and 'spill' into the plasma.

Acute Disease↗
PubMed1996

Roles of gall bladder emptying and intestinal transit in the pathogenesis of octreotide induced gall bladder stones.

BACKGROUND: Octreotide treatment of acromegalic patients increases the % deoxycholic acid conjugates and the cholesterol saturation of gall bladder bile, and induces gall stone formation. AIMS: To study the roles of gall bladder emptying and intestinal transit in these phenomena. METHODS AND PATIENTS: Gall bladder emptying and mouth to caecum transit was measured in (a) control subjects and acromegalic patients given saline or 50 micrograms of octreotide, and (b) acromegalic patients taking long term octreotide. In the second group, large bowel transit was also measured. RESULTS: A single dose of octreotide inhibited meal stimulated gall bladder emptying, the ejection fraction falling from mean (SEM) 66.0 (2.3)% to 7.0 (5.3)% in controls (p < 0.001); from 72.5 (2.1) to 16.6 (5.1)% in untreated acromegalic patients (p < 0.001), and to 30.4 (9.5)% in acromegalic patients taking long term octreotide (p < 0.001 v untreated acromegalic group). Octreotide prolonged mouth to caecum transit time, from 112 (15) min to 237 (13) min in controls (p < 0.001), from 170 (13) min to 282 (11) min in untreated acromegalic patients (p < 0.001), and to 247 (10) min in acromegalic patients taking long term octreotide (p < 0.001 v untreated acromegalic patients). The mean large bowel transit in octreotide untreated compared with treated acromegalic patients remained unchanged (40 (6) h v 47 (6) h). CONCLUSIONS: Prolongation of intestinal transit and impaired gall bladder emptying may contribute to lithogenic changes in bile composition and gall stone formation in patients receiving long term octreotide.

Acromegaly↗
PubMed1995

Gallbladder stone recurrence after medical treatment. Do gallstones recur true to type?

Medical treatments that dissolve or remove gallbladder stones but leave the gallbladder in situ have the disadvantage of gallstone recurrence. Little is known about the composition of recurrent stones or whether they recur true to type. In 21 patients with recurrent stones detected 5-74 months (mean +/- SEM, 26 +/- 4 months) after being rendered stone-free with dissolution therapy (N = 15) or percutaneous cholecystolithotomy (N = 6), we compared pretreatment and postrecurrence gallstone number, maximum gallstone attenuation scores measured by computed tomography (CT) and, in 13, the dissolvability of the recurrent stones with oral bile acids +/- extracorporeal shock-wave lithotripsy. Before treatment, five patients had solitary and 16 had multiple stones but on recurrence, the gallstones differed in number from the primary stones in 10 of the 21 patients. As a result of patient selection, before dissolution, the primary stones were all radiolucent with maximum CT scores of < 100 Hounsfield units (HU) (mean 45, range 10-84 HU). On recurrence, the stones were again CT-lucent in 13 of the 15 patients but were CT-dense in the remaining two (118 and 176 HU). Initially, all six patients treated by percutaneous cholecystolithotomy had radio-opaque stones, with a mean CT score of 459 (range 100-969) HU. However, on recurrence, only one had calcified stones (HU 140); the remaining five had CT-lucent stones (16-98 HU, P < 0.05). Of the 13 patients whose recurrent, plain x-ray-lucent and CT-lucent stones were treated with oral bile acids +/- lithotripsy, 12 (92%) showed evidence of gallstone dissolution. We conclude that gallbladder stones do not recur true to type in up to two thirds of patients. However, irrespective of original gallstone composition, recurrent stones are usually radio- and CT-lucent, presumed cholesterol-rich, and therefore potentially dissolvable with oral bile acids.

Bile Acids and Salts↗
PubMed1995

Effect of acute bile acid pool depletion on total and ionized calcium concentrations in human bile.

Although calcium salts are important components of gallstones, there are few data on the total and ionized calcium content of human bile. Therefore, in 14 fasting T-tube patients studied 7-11 days after cholecystectomy, we measured bile flow, bile acid [BA], total [CaTOT] and free ionized [Ca++] calcium concentrations, in 20-30 min bile collections during acute BA pool depletion induced by 6-8 h of continuous bile drainage. During washout of the BA pool there were parallel falls in bile flow, BA output and total calcium output (correlation coefficients ranging from 0.59 to 0.99; P < 0.02-0.001). In 12 of the 14 patients, [CaTOT] also fell (from 1.84 +/- 0.29 to 1.32 +/- 0.34 mmol L-1) in parallel with [BA] (from 34.0 +/- 14.0 to 8.2 +/- 8.0 mmol L-1; r = 0.75-0.98; P < 0.005). In contrast, biliary [Ca++] remained virtually unchanged. These data suggest that the BAs are linked to the bound, rather than to the free, ionized, fraction of biliary calcium, which is consistent with in vivo calcium binding by BAs. A model is proposed in which BA-induced biliary calcium secretion results from (i) bile acid-induced water flow via solvent drag; and (ii) calcium binding in the bile canaliculus by bile acids, which induces paracellular diffusion of Ca++, thereby maintaining [Ca++] independent of [BA].

Adult↗
PubMed1995

Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.

Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.

Acromegaly↗
PubMed1995

Ultrasound-guided percutaneous fine needle puncture of the gallbladder for studies of bile composition.

Ultrasound-guided percutaneous fine needle puncture of the gallbladder (PFNP-GB) is invaluable for diagnostic and research purposes, but there are few reports about its safety. We therefore describe the efficacy and side-effects of 43 consecutive gallbladder punctures in 39 patients. PFNP-GB was successful in 40/43 (93%), but failed in three. Bile was completely aspirated in 28 of the 40 (70%) successful procedures. After 36 of the 43 punctures (84%), the patients remained asymptomatic, although on seven occasions (16%) the patients complained of right upper quadrant pain 0.5-12 h after the procedure. In six of these, the pain resolved in 2-24 h, although one developed a leucocytosis (22 x 10(9) 1(-1)). The seventh patient developed pyrexia and signs of generalized peritonism, which settled with conservative therapy. Ultrasonographic abnormalities of the gallbladder wall were seen in five of the seven symptomatic patients, consisting of: (i) an increase in the thickness of the gallbladder wall (n = 5) from less than 2 mm to 4-14 mm; (ii) peri-cholecystic collections (n = 2) measuring 5 and 11 mm in diameter; (iii) an intraluminal mucosal flap (n = 1); (iv) an intraluminal echogenic layer (n = 1); and (v) a 12 cm intraabdominal haematoma in the patient with generalized peritonism. Predictors of pain were: (i) the number of needle "passes" (3.7 +/- 0.8, range 2-8, in patients with pain vs 2.0 +/- 0.2, range 1-6, in pain-free patients, p < 0.02); (ii) the absence of gallbladder stones (p < 0.03); and (iii) incomplete aspiration of bile from the gallbladder (p < 0.02). PFNP-GB is an effective way of sampling fresh gallbladder bile, although there is a 16% risk of inducing pain and/or ultrasonographic changes in the gallbladder.

Adult↗
PubMed1995

Percutaneous cholecystolithotomy: risks, benefits, and long-term outcome.

BACKGROUND: For symptomatic patients with gallbladder stones and a patent cystic duct who wish to retain their 'functioning' gallbladders, percutaneous cholecystolithotomy (PCCL) offers an alternative to open or laparoscopic cholecystectomy. However, there are few data on the risks and benefits of this approach or on the long-term outcome. METHODS AND RESULTS: In 21 patients with symptomatic calcified gallstones, PCCL was successful (gallstone clearance) in 17 (81%). Four to 62 (median, 35) months after clearance 9 of the 17 remained symptom-free and stone-free, whereas 4 developed biliary sludge at 7, 30, 32, and 35 months, 2 of whom subsequently developed gallstones. In four other patients gallstones recurred without evidence of preceding biliary sludge at 9, 16, 19, and 27 months, corresponding to an actuarial gallstone recurrence rate at 36 months of 53.4 +/- SEM 15.1%, and a combined stone/sludge recurrence rate of 63.4 +/- 13.5%. CONCLUSIONS: PCCL is moderately effective but, because of the frequency of complications and sludge/stone recurrence, is likely to have only a limited residual role in the era of laparoscopic cholecystectomy.

Cholecystostomy↗
PubMed1995

Deoxycholic acid influences cholesterol solubilization and microcrystal nucleation time in gallbladder bile.

Little is known about the effects of biliary deoxycholic acid on the partitioning of biliary cholesterol between vesicles and micelles and on the rate of nucleation of cholesterol microcrystals, key steps in gallstone formation. Therefore, 43 samples of fresh gallbladder bile were obtained from a heterogeneous group of patients with and without stones. Univariate and multivariate analyses were then applied to determine the inter-relationships between biliary cholesterol saturation, total lipid concentration, and bile acid species and (1) the distribution of biliary cholesterol between vesicles and micelles and (2) the cholesterol microcrystal nucleation time. The percentage of deoxycholic acid in bile was shown to be linearly related to the cholesterol saturation index (r = .54; P < .001), the vesicular cholesterol:phospholipid molar ratio (r = .53; P < .001), and the molar concentration of cholesterol in the vesicles (r = .59; P < .001). The mean proportion of biliary deoxycholic acid conjugates was also greater in patients with rapid nucleation times (23.4 +/- SEM 1.1%) than in those with slow nucleation times (17.3 +/- 1.9%; P < .05). As total bile lipid concentration increased, the proportion of total biliary cholesterol in vesicles decreased (r = .53; P < .001), whereas the molar concentration of vesicular cholesterol increased (r = .42, P < .01). The cholesterol saturation indices, total bile lipid concentration, and proportion of biliary deoxycholate were independent determinants of the molar concentration of cholesterol in vesicles. We conclude that relative increases in the percentage of deoxycholic acid and in bile lipid concentration, favor the partitioning of cholesterol into vesicles. In turn, this leads to an increase in the vesicular cholesterol:phospholipid molar ratio and thus to a decrease in the cholesterol microcrystal nucleation time.

Adult↗
PubMed1994

Gastric mucosal toxicity of duodenal juice constituents in the rat. Acute studies using ex vivo rat gastric chamber model.

To determine the acute gastrotoxicity of refluxed duodenal contents, an ex vivo rat gastric chamber was used to study mucosal damage produced by conjugated and unconjugated human bile acids and lysolecithin at neutral and acidic pH; the effects of trypsin, human duodenal aspirate, and combinations of chenodeoxycholic acid, lecithin, and lysolecithin were also studied. At neutral pH, all bile acids except tauroursodeoxycholic acid, caused dose-dependent falls in mucosal potential difference and losses of mucosal nucleic acid into the chamber fluid, indicating mucosal damage. The di-alpha-hydroxy bile acids, deoxycholic and chenodeoxycholic acids, were more gastrotoxic than cholic and ursodeoxycholic acids, and all unconjugated bile acids were more toxic than their conjugated species, none of which produced damage at concentrations below 2.0 mM. For all but the taurine conjugates, bile acid-induced changes in potential difference were lower at acidic then at neutral pH. Lysolecithin gastrotoxicity, comparable at neutral pH to that of chenodeoxycholic acid, was also reduced at acidic pH. Lecithin decreased the gastrotoxicity of chenodeoxycholic acid and lysolecithin. Trypsin produced no damage, and the gastrotoxicity of human duodenal aspirate was unaffected by prior heat inactivation of pancreatic enzymes.

Analysis of Variance↗
PubMed1994

The role of bile composition and physical chemistry in the pathogenesis of octreotide-associated gallbladder stones.

BACKGROUND/AIMS: Treatment of acromegaly with octreotide inhibits cholecystokinin release and gallbladder contraction and induces gallbladder stones. However, little is known about the effects of octreotide on bile composition. METHODS: Fresh gallbladder bile was obtained from three groups: (1) 11 nonacromegalic patients with cholesterol gallstones, (2) 6 acromegalic patients with octreotide-associated stones (treatment, 300-600 micrograms/day for 3-66 months), and (3) 8 acromogalic patients with no stones before octreotide treatment, 5 of whom were reexamined after 3-24 months of therapy. RESULTS: Compared with stone-free acromegalic patients untreated with octreotide, bile from patients with cholesterol stones and from acromegalic patients with octreotide-associated stones had greater saturation indices (mean +/- SEM) (1.52 +/- 0.17 and 1.32 +/- 0.14 vs. 0.90 +/- 0.05, respectively; P < 0.01); more cholesterol in vesicles (61.2% +/- 4.5% and 67.7% +/- 7.2% vs. 37.7% +/- 3.5%; P < 0.009); more unstable vesicles (cholesterol/phospholipid ratios, 0.97 +/- 0.12 and 0.81 +/- 0.16 vs. 0.52 +/- 0.05; P < 0.02); more rapid nucleation (< 5 and < 5 days vs. > 18 days; P < 0.003); and more deoxycholic acid (22.8% +/- 2.4% and 23.6% +/- 4.8% vs. 13.9% +/- 1.4%; P < 0.05). In the paired studies, the saturation indices increased from 0.89 +/- 0.07 before octreotide treatment to 1.12 +/- 0.03 during octreotide treatment (P < 0.02), as did the percentage of deoxycholic acid from 13.3% +/- 2.1% to 24.9% +/- 2.7% (P < 0.03). CONCLUSIONS: Acromegalic patients with octreotide-associated gallstones and stone-free acromegalic patients treated with octreotide have similar changes in bile composition to those in patients with "conventional" cholesterol gallstone disease.

Acromegaly↗
PubMed1994

Changes in serum calcium levels influence biliary calcium levels in humans.

BACKGROUND/AIMS: There are few data on the influence of serum calcium on biliary total and ionized calcium levels in humans. The aims of the study were to increase serum calcium levels short-term by intravenous calcium infusion and study the resultant changes in total and ionized calcium concentrations ([CaTOT] and [Ca2+]) in T-tube bile. METHODS: Serum and biliary total and ionized calcium concentrations were measured over an 8-hour period in 7 postcholecystectomy patients with T tubes before, during, and after a 4-hour intravenous infusion of 10% calcium gluconate. RESULTS: During the infusion, serum [CaTOT] increased from 2.08 +/- 0.14 mmol/L (mean +/- SD) to 3.18 +/- 0.33 mmol/L, and serum [Ca2+] increased from 1.13 +/- 0.13 mmol/L to 1.68 +/- 0.13 mmol/L. After a 20-40-minute time lag, there were corresponding increases in biliary [CaTOT] from 1.90 +/- 0.45 mmol/L to 2.80 +/- 0.52 mmol/L and in biliary [Ca2+] from 0.70 +/- 0.11 mmol/L to 1.19 +/- 0.16 mmol/L. When the data were pooled, serum [Ca2+] showed significant correlations with both biliary [CaTOT] (n = 128; r = 0.56; P < 0.001) and biliary [Ca2+] (n = 128; r = 0.64; P < 0.001). CONCLUSIONS: These results support the hypothesis that the biliary tree is freely permeable to calcium ions and that serum calcium level is one determinant of biliary calcium concentration. Our data may also explain the observation that patients with hypercalcemia are reported to have a greater than normal prevalence of calcified gallstones.

Aged↗
PubMed1993

Enhanced growth of small bowel in transgenic mice overexpressing bovine growth hormone.

BACKGROUND: Transgenic mice with a bovine growth hormone gene linked to a mouse metallothionein I promoter (growth hormone transgenics) are a model of chronic growth hormone excess. METHODS: Growth of small bowel mucosa in ad libitum-fed growth hormone transgenics and wild type littermates and in growth hormone transgenics pair fed with wild-type littermates were compared. RESULTS: In both groups, body weight and small bowel weight were greater in growth hormone transgenics. Similarly, mucosal mass was 50%-100% greater in growth hormone transgenics, and the effect was greatest in proximal bowel. Villus height, measured in jejunum, was also greater in growth hormone transgenics. Measurements of mucosal proliferation did not differ between the growth hormone transgenics and wild type. Abundance of insulin-like growth factor-I messenger RNA in bowel was greater in growth hormone transgenics. CONCLUSIONS: Chronic growth hormone excess results in increased growth of small bowel mucosa. This effect appears to be specific because it occurred in ad libitum-fed and diet-restricted growth hormone transgenics, influenced villus height, and was more pronounced in upper than lower small bowel. The effect of chronic growth hormone excess does not appear to be secondary to an increase in the rate of mucosal proliferation, suggesting an effect on lifespan of mucosal cells.

Animals↗
PubMed1993

Gall stone recurrence and its prevention: the British/Belgian Gall Stone Study Group's post-dissolution trial.

The British/Belgian Gall Stone Study Group (BBGSG) post-dissolution trial was a prospective, multicentre, randomised, double blind trial of: (i) low dose ursodeoxycholic acid, (ii) placebo, and (iii) a high fibre, low refined carbohydrate diet in the prevention of gall stone recurrence in patients with complete gall stone dissolution. Further aims included establishing the timing and frequency of recurrence and its association with biliary symptoms, a comparison of the sensitivity of ultrasonography v oral cholecystectography in detecting recurrent stones, and a search for risk factors predicting recurrence. Ninety three patients entered the study, and 82 were followed up for up to five years (mean (SEM) 28 (1.5) months) with six monthly ultrasonography and yearly oral cholecystectography. There were 21 recurrences (26 by oral cholecystectography or ultrasonography, or both), only two of which were symptomatic, which were detected between 12 and 42 months after trial entry. This corresponded to an actuarial recurrence rate of 33.9 (7.0%) by lifetable analysis at 42 months and subsequently. There were four recurrences in the ursodeoxycholic acid, six in the placebo, and 11 in the diet groups, corresponding to 21.9 (9.9)%, 27.4 (10.1)%, and 45.8 (12.4)% respectively at 42 months by lifetable analysis (NS). Variables including age, obesity, menopausal state, pregnancy, and oestrogen containing drugs were not shown to affect recurrence rate. Men had more frequent recurrence than women (NS). Patients who had had multiple stones experienced more recurrences than did those with single stones (NS). Recurrence did not occur in patients who took non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.02). The stone free interval between stone dissolution and trial entry proved to be important--those stone free > nine months had a recurrence rate of only 12.7 (6.0)% at 42 months compared with 55.4 (12.5)% in those stone free < nine months (p < 0.01). There was imbalance between the ursodeoxycholic acid and placebo groups for this factor, and after applying a statistical correction, the adjusted recurrence rate in the ursodeoxycholic acid group was 15% compared with 30% in both placebo and diet groups (NS). These data suggest that after medical dissolution, the risk of gall stone recurrence is not reduced by a high fibre, low refined carbohydrate diet: it may be lowered, but not abolished, by low dose ursodeoxycholic acid.

Adult↗